Antidepressants and ∝-adrenoceptors

Pinder, Roger M.

doi:10.1007/978-1-349-06671-1_24

Cited by 6 publications

(1 citation statement)

References 63 publications

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“…A common problem associated with the current antidepressant therapies is the several side effects, e.g., clinically useful antidepressant agents produce withdrawal syndromes, except agomelatine [6]. Classical antidepressants like monoamine oxidase (MAO) inhibitors and tricyclic antidepressants produce drug-drug/-food interactions, anticholinergic, and cardiovascular side effects [7,8]. Besides all currently approved antidepressant drugs for example, selective serotonin reuptake inhibitors (SSRIs) have slow onset of action, since there is a delay of about 4-6 weeks to alleviate the symptoms [9].…”

Section: Introductionmentioning

confidence: 99%

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT₃ Receptor Antagonists with Antidepressant‐Like Activity

Dhar

Mahesh

Jindal

et al. 2015

Archiv der Pharmazie

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Series of piperazine analogs of naphthyridine-3-carboxamides and indole-2-carboxamides were designed using a ligand-based approach with consideration of the pharmacophoric requirements for 5-HT3 receptor antagonists. The title carboxamides were synthesized using appropriate synthetic routes. Initially, the 5-HT3 receptor antagonistic activity of all the compounds was determined on isolated guinea pig ileum tissue against the 5-HT3 agonist, 2-methyl-5-hydroxytryptamine, which was denoted in the form of pA2 values. The structure-activity relationship regarding the influence of the aromatic part and basic moiety as features in the 5-HT3 pharmacophore was derived. Among all the compounds screened, the piperazine derivatives of indole-2-carboxamide 13i and naphthyridine-3-carboxamide 8h exhibited prominent 5-HT3 receptor antagonism with pA2 values of 7.5 and 7.3, respectively. Subsequent investigation of the antidepressant activities of selected compounds in the mouse forced swim test (FST) led to the identification of the piperazine analogs of indole-2-carboxamide 13i and naphthyridine-3-carboxamide 8h as the most promising compounds. Both 13i and 8h demonstrated significant reduction in the duration of immobility as compared to the control. Importantly, none of the tested compounds affected the baseline locomotion of mice at the tested dose levels.

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Section: Introductionmentioning

confidence: 99%

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT₃ Receptor Antagonists with Antidepressant‐Like Activity

Dhar

Mahesh

Jindal

et al. 2015

Archiv der Pharmazie

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Is there a therapeutic window for plasma concentration of mianserin plus desmethylmianserin?

Otani

Kaneko

Sasa

et al. 1991

Human Psychopharmacology

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The relationship between clinical effects and plasma concentrations of mianserin and desmethylmianserin was studied in 29 cases of major depression during 3 weeks of mianserin treatment. The daily dose of mianserin was 30 mg in 27 cases and 20 mg in two cases. There was a significant U-shaped relationship between the final Montgomery Asberg Depression Rating Scale (MADRS) score and the steady-state plasma concentration of mianserin (p < 0.05) or desmethylmianserin (p < 0.05). A much stronger relationship was observed for mianserin plus desmethylmianserin @<0.001). A theoretical therapeutic window (where a final MADRS score was expected to be 10 or less) was 71-128 nmol/l for mianserin, 34-61 nmol/l for desmethylmianserin, and 101-183 nmol/l for mianserin plus desmethylmianserin. The proportion of responders was significantly higher inside than outside the window for mianserin plus desmethylmianserin (p =0,0033), but not for mianserin (p =0.063) or for desmethylmianserin (p =0.077). The occurrence of subjective side-effects was not dependent on the plasma concentrations of these compounds. The present study suggests that desmethylmianserin contributes substantially to the overall antidepressant effects of mianserin treatment, and that the therapeutic response is most dependent on the combined plasma concentration of mianserin and desmethylmianserin, with an optimal therapeutic response occurring in the intermediate range.

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The effect of mianserin hydrochloride on delirium

Nakamura

Uchimura

Yamada

et al. 1995

Human Psychopharmacology

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Mianserin HCI (1&60 mg/day) was administered orally before bedtime to 46 patients (mean age: 63 years) with delirium at Kurume University Hospital. The therapeutic effects of mianserin were assessed pre-and post-treatment using the Delirium Rating Scale (DRS: Trzepacz et al., 1988). The mean pre-treatment DRS score was 21. This score decreased significantly (p <0-05) to 14 on treatment day 1 and 10 on day 3. Mianserin was observed to be effective in 85 per cent of the cases (marked improvement in 67 per cent of the patients and slight improvement in 17 per cent). Of the 46 patients, 28 were classified with delirium due to direct causes such as a brain turnour or cerebrovascular disease, and 18 due to facilitating factors such as hospitalization or physical restraint. In the former group, marked improvement was observed in 54 per cent of the patients, and slight improvement in 21 per cent. The latter group demonstrated marked improvement in 89 per cent of the patients, and slight improvement in 11 per cent. In control subjects receiving haloperidol, marked improvement was observed in 62 per cent of I7 delirious patients. The plasma concentration of mianserin reached a therapeutic level within 24 h of the initiation of treatment. Hence, based on these clinical results and on measurements of plasma mianserin concentrations, mianserin can be considered effective in the treatment of delirium in elderly patients due to its rapid onset and few side-effects. Mianserin may offer an efficacy similar to that of haloperidol in the treatment of delirium while being safer.

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Antidepressants and ∝-adrenoceptors

Cited by 6 publications

References 63 publications

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT₃ Receptor Antagonists with Antidepressant‐Like Activity

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT₃ Receptor Antagonists with Antidepressant‐Like Activity

Is there a therapeutic window for plasma concentration of mianserin plus desmethylmianserin?

The effect of mianserin hydrochloride on delirium

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Antidepressants and ∝-adrenoceptors

Cited by 6 publications

References 63 publications

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT3 Receptor Antagonists with Antidepressant‐Like Activity

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT3 Receptor Antagonists with Antidepressant‐Like Activity

Is there a therapeutic window for plasma concentration of mianserin plus desmethylmianserin?

The effect of mianserin hydrochloride on delirium

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Product

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Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT₃ Receptor Antagonists with Antidepressant‐Like Activity

Piperazine Analogs of Naphthyridine‐3‐carboxamides and Indole‐2‐carboxamides: Novel 5‐HT₃ Receptor Antagonists with Antidepressant‐Like Activity